Adherent device with multiple physiological sensors

ABSTRACT

An adherent device to monitor a patient comprises an adhesive patch to adhere to a skin of the patient, and at least four electrodes connected to the patch and capable of electrically coupling to the patient. The adherent device further includes impedance circuitry coupled to the at least four electrodes to measure a hydration signal of the patient and electrocardiogram circuitry coupled to at least two of the at least four electrodes to measure an electrocardiogram signal of the patient.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit under 35 USC 119(e) of U.S.Provisional Application No. 60/972,537 and 60/972,629 both filed Sep.14, 2007, and 61/055,645 and 61/055,666 both filed May 23, 2008; thefull disclosures of which are incorporated herein by reference in theirentirety.

The subject matter of the present application is related to thefollowing applications: 60/972,512; 60/972,329; 60/972,354; 60/972,616;60/972,363; 60/972,343; 60/972,581; 60/972,316; 60/972,333; 60/972,359;60/972,336; 60/972,340 all of which were filed on Sep. 14, 2007;61/046,196 filed Apr. 18, 2008; 61/047,875 filed Apr. 25, 2008;61/055,656 and 61/055,662 both filed May 23, 2008; and 61/079,746 filedJul. 10, 2008.

The following applications are being filed concurrently with the presentapplication, on Sep. 12, 2008: Attorney Docket Nos. 026843-000110USentitled “Multi-Sensor Patient Monitor to Detect Impending CardiacDecompensation Prediction”; 026843-000410US entitled “Injectable Devicefor Physiological Monitoring”; 026843-000510US entitled “Delivery Systemfor Injectable Physiological Monitoring System”; 026843-000620USentitled “Adherent Device for Cardiac Rhythm Management”;026843-000710US entitled “Adherent Device for Respiratory Monitoring”;026843-000810US entitled “Adherent Athletic Monitor”; 026843-000910USentitled “Adherent Emergency Monitor”; 026843-001320US entitled“Adherent Device with Physiological Sensors”; 026843-001410US entitled“Medical Device Automatic Start-up upon Contact to Patient Tissue”;026843-001900US entitled “System and Methods for Wireless Body FluidMonitoring”; 026843-002010US entitled “Adherent Cardiac Monitor withAdvanced Sensing Capabilities”; 026843-002410US entitled “AdherentDevice for Sleep Disordered Breathing”; 026843-002710US entitled“Dynamic Pairing of Patients to Data Collection Gateways”;026843-003010US entitled “Adherent Multi-Sensor Device with ImplantableDevice Communications Capabilities”; 026843-003110US entitled “DataCollection in a Multi-Sensor Patient Monitor”; 026843-003210US entitled“Adherent Multi-Sensor Device with Empathic Monitoring”; 026843-003310USentitled “Energy Management for Adherent Patient Monitor”; and026843-003410US entitled “Tracking and Security for Adherent PatientMonitor.”

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to patient monitoring. Althoughembodiments make specific reference to monitoring impedance andelectrocardiogram signals with an adherent patch, the system methods anddevice described herein may be applicable to many applications in whichphysiological monitoring is used, for example wireless physiologicalmonitoring for extended periods.

Patients are often treated for diseases and/or conditions associatedwith a compromised status of the patient, for example a compromisedphysiologic status. In some instances, a patient may report symptomsthat require diagnosis to determine the underlying cause. For example, apatient may report fainting or dizziness that requires diagnosis, inwhich long term monitoring of the patient can provide useful informationas to the physiologic status of the patient. In some instances a patientmay have suffered a heart attack and require care and/or monitoringafter release from the hospital. One example of a device to provide longterm monitoring of a patient is the Holter monitor, or ambulatoryelectrocardiography device.

In addition to measuring heart signals with electrocardiograms, knownphysiologic measurements include impedance measurements. For example,transthoracic impedance measurements can be used to measure hydrationand respiration. Although transthoracic measurements can be useful, suchmeasurements may use electrodes that are positioned across the midlineof the patient, and may be somewhat uncomfortable and/or cumbersome forthe patient to wear.

Work in relation to embodiments of the present invention suggests thatknown methods and apparatus for long term monitoring of patients may beless than ideal. At least some of the known devices may not collect theright kinds of data to treat patients optimally. For example, althoughsuccessful at detecting and storing electrocardiogram signals, devicessuch as the Holter monitor can be somewhat bulky and may not collect allof the kinds of data that would be ideal to diagnose and/or treat apatient. In at least some instances, devices that are worn by thepatient may be somewhat uncomfortable, which may lead to patients notwearing the devices and not complying with direction from the healthcare provider, such that data collected may be less than ideal. Althoughimplantable devices may be used in some instances, many of these devicescan be invasive and/or costly, and may suffer at least some of theshortcomings of known wearable devices.

Therefore, a need exists for improved patient monitoring. Ideally, suchimproved patient monitoring would avoid at least some of theshort-comings of the present methods and devices.

2. Description of Background Art

The following U.S. patents and Publications may describe relevantbackground art: U.S. Pat. Nos. 3,370,459; 3,805,769; 3,845,757;3,972,329; 4,121,573; 4,141,366; 4,838,273; 4,955,381; 4,981,139;5,080,099; 5,353,793; 5,511,553; 5,544,661; 5,558,638; 5,724,025;5,772,586; 5,862,802; 6,047,203; 6,117,077; 6,129,744; 6,225,901;6,385,473; 6,416,471; 6,454,707; 6,527,711; 6,527,729; 6,551,252;6,595,927; 6,595,929; 6,605,038; 6,645,153; 6,795,722; 6,821,249;6,980,851; 7,020,508; 7,054,679; 7,153,262; 2003/0092975; 2005/0113703;2005/0131288; 2006/0010090; 2006/0031102; 2006/0089679; 2006/0155183;2006/122474; 2006/0224051; 2006/0264730; 2007/0021678; and 2007/0038038.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to patient monitoring. Althoughembodiments make specific reference to monitoring impedance andelectrocardiogram signals with an adherent patch, the system methods anddevice described herein may be applicable to any application in whichphysiological monitoring is used, for example wireless physiologicalmonitoring for extended periods.

In a first aspect, embodiments of the present invention provide anadherent device to monitor a patient. The device comprises an adhesivepatch to adhere to a skin of the patient. At least four electrodes areconnected to the patch and capable of electrically coupling to thepatient. Impedance circuitry can be coupled to the at least fourelectrodes to measure a hydration signal of the patient.Electrocardiogram circuitry can be coupled to at least two of the atleast four electrodes to measure an electrocardiogram signal of thepatient. An accelerometer can be mechanically coupled, for exampleadhered or affixed, to the adhesive patch to generate an accelerometersignal in response to at least one of an activity or a position of thepatient. Work in relation to embodiments of the present inventionsuggests accelerometer signals can improve patient diagnosis, and can beespecially useful when used with other signals, such aselectrocardiogram signals and impedance signals for hydration andrespiration. Mechanically coupling the accelerometer to the electrodesfor measuring impedance and hydration may also improve the qualityand/or usefulness of the impedance and/or electrocardiogram signals. Forexample, mechanical coupling of the accelerometer to the electrodes andto the skin of the patient can improve the reliability, quality and/oraccuracy of the accelerometer measurements, as the electrode signals canindicate the quality of mechanical coupling of the patch to the patientso as to indicate that the device is connected to the patient and thatthe accelerometer signals are valid. In some embodiments, the adherentdevice may comprise a dimension across that is no more than about 8inches, such that the device can be comfortably worn by at least somepatients for an extended period to permit collection of theelectrocardiogram, impedance and accelerometer signals for extendedperiods.

In many embodiments, the adhesive patch is mechanically coupled to theat least four electrodes, the impedance circuitry, the electrocardiogramcircuitry and the accelerometer, such that the patch is capable ofsupporting the at least four electrodes, the impedance circuitry, theelectrocardiogram circuitry and the accelerometer when the adherentpatch is adhered to the skin of the patient.

In many embodiments, a wireless communication circuitry is coupled tothe impedance circuitry, the electrocardiogram circuitry and theaccelerometer to transmit to a remote center with a communicationprotocol at least one of the hydration signal, the electrocardiogramsignal or the accelerometer signal. The wireless communication circuitrycan be configured to transmit the hydration signal, theelectrocardiogram signal and the accelerometer signal to the remotecenter with a single wireless hop from the wireless communicationcircuitry to an intermediate device. In specific embodiments, thecommunication protocol can comprise at least one of Bluetooth, Zigbee,WiFi, WiMax, IR, a cellular protocol, amplitude modulation or frequencymodulation. In many embodiments, the intermediate device comprises adata collection system to collect and/or store data from the wirelesstransmitter, and the data collection system can be configured tocommunicate periodically with the remote center with wirelesscommunication and/or wired communication. The communications protocolmay comprise a two way protocol such that the remote center is capableof issuing commands to control data collection

The adherent device may comprise many sensors configured to measure manydifferent signals. In many embodiments, the accelerometer comprises atleast one of a piezoelectric accelerometer, capacitive accelerometer orelectromechanical accelerometer and wherein the accelerometer comprisesa 3-axis accelerometer to measure at least one of an inclination, aposition, an orientation or acceleration of the patient in threedimensions. The impedance circuitry can be adapted to measureextracellular fluid of the patient with at least one frequency within arange from about 0.5 kHz to about 200 kHz., and the impedance circuitryis configured to determine a respiration of the patient. The device maycomprise a microphone to detect an audio signal from within the patient,and the audio signal may comprise a heart sound with an S3 heart soundand/or a respiratory sound with rales and/or crackles. The device maycomprise a temperature sensor to measure a temperature of the patient.Work in relation to embodiments of the present invention suggest thatpatient temperature may effect impedance measurements, such that theimpedance measurements can be corrected with the temperaturemeasurement.

In many embodiments, the adherent device comprises a processorcomprising a tangible medium, and the processor is configured to controla collection and transmission of data from the impedance circuitry, theelectrocardiogram circuitry and the accelerometer. The adherent devicemay comprise a real time clock and a frequency generator.

In another aspect, embodiments of the present invention provide a methodof monitoring a patient. An adhesive patch is adhered to a skin of thepatient to couple at least four electrodes to the skin of the patient. Ahydration signal of the patient is measured with impedance circuitrycoupled to the at least four electrodes. An electrocardiogram signal ofthe patient is measured with electrocardiogram circuitry coupled to atleast two of the at least four electrodes. A signal from anaccelerometer is measured in response to at least one of an activity ora position of the patient.

In many embodiments, the adhesive patch supports the at least fourelectrodes, the impedance circuitry, the electrocardiogram circuitry andthe accelerometer when the adherent patch is adhered to the skin of thepatient.

In another aspect, embodiments of the present invention provide anadherent device to monitor a patient. The adherent device comprises anadhesive patch to adhere to a skin of the patient. At least fourelectrodes are affixed to the patch and capable of electrically couplingto the patient. A maximum dimension across the at least 4 electrodes maycomprise no more that about eight inches, such that the at least fourelectrodes are capable of adhering to either a left side or a right sideof the patient. Impedance circuitry may be coupled to the at least fourelectrodes to measure hydration of the patient. Electrocardiogramcircuitry may be coupled to at least two of the at least four electrodesto measure an electrocardiogram of the patient.

In many embodiments, the maximum distance across the at least fourelectrodes comprises no more than about six inches. The device comprisesa maximum dimension across no more than about 8 inches, and the patch iscapable of measuring the electrocardiogram and the impedance from a leftside or a right side of the patient.

In another aspect, an adherent device to monitor a patient for anextended period is provided. The device comprises a breathable tapecomprising an adhesive coating to adhere the breathable tape to a skinof the patient, such that tape and device may be comfortable when wornby the patient. The breathable tape may comprise a porous material, forexample a porous fabric, to allow transmission of water vapor while thedevice is worn by the patient. At least one electrode is affixed to thebreathable tape and capable of electrically coupling to a skin of thepatient. At least one gel can be disposed over a contact surface of theat least one electrode to electrically connect the electrode to theskin. A printed circuit board, for example, a flex printed circuitboard, can be connected to the breathable tape to support the printedcircuit board with the breathable tape when the tape is adhered to thepatient. Electronic components may be electrically connected to theprinted circuit board and coupled to the at least one electrode tomeasure physiologic signals of the patient. A breathable cover, whichmay be water resistant, can be disposed over the circuit board andelectronic components and connected to at least one of the electronicscomponents, the printed circuit board or the breathable tape.

In many embodiments, an electronics housing is adhered to at least oneof the electronics circuitry or the printed circuit board, such that theelectronics housing is disposed between the cover and the electronicscomponents.

In many embodiments, a gel cover is positioned over a breathable tape toinhibit a flow of the gel through the breathable tape. The printedcircuit board, for example a flex printed circuit board, may be locatedover the gel cover such that the gel cover is disposed between thebreathable tape and the printed circuit board.

In many embodiments, the breathable tape comprises a first porosity, andthe gel cover comprises a breathable tape with a second porosity, inwhich the second porosity is less than the first porosity to inhibitflow of the gel through the breathable tape. In specific embodiments,the breathable tape comprises a tricot-knit polyester fabric backingwith an acrylate adhesive coating, and the gel cover comprises apolyurethane, non-woven backing with an acrylate adhesive coating.

In many embodiments, the breathable tape, the adhesive coating, the atleast one electrode and gel coating are separable from the printedcircuit board, electronic components, and water resistant housing andcover, such that the printed circuit board, electronic components, waterresistant housing and water proof cover are reusable.

In many embodiments, the at least one electrode extends through at leastone aperture in the breathable tape. In some embodiments, the at leastone electrode is configured to electrically couple to the printedcircuit board through the breathable tape.

In another aspect, embodiments of the present invention provide a methodof monitoring a patient for an extended period. An electronics module isattached to a first adherent patch component of a plurality of adherentpatch components. The first adherent patch component is adhered to askin of the patient. The electronics module is removed from the firstadherent patch component. The electronics module is attached to a secondpatch component of the plurality of patch components after the firstadherent patch component has been removed.

In many embodiments, the electronics module is removed from the secondadherent patch component, and the electronics module is attached to athird patch component of the plurality of patch components after thesecond adherent patch component has been removed.

In many embodiments, impedance signals are measured when the thirdadherent patch component is adhered to the patient.

In another aspect, embodiments of the present invention provide a systemto monitor a patient for an extended period. The system comprise aplurality of adherent patch components. An electronics module may beadapted to couple to each of the plurality of patch components forsequential measurements from each of the patch components.

In many embodiments, each of the plurality of adherent patch componentscomprises, a breathable tape with an adhesive coating to adhere thebreathable tape to a skin of the patient, and at least one electrodeaffixed to the breathable tape.

In many embodiments, the electronics module comprises a printed circuitboard configured to connect electrically to the at least one electrodeto measure physiologic signals of the patient, electronic componentselectrically connected to the printed circuit board, and a housingadhered to at least one of the electronics module or the printed circuitboard.

In another aspect, embodiments of the present invention provide a methodof monitoring a patient for an extended period of time. A first adherentpatch is adhered on a first side of the patient, in which the firstadherent patch comprises first electrodes to measure at least one of anelectrocardiogram or an impedance. The at least one of theelectrocardiogram or the impedance is measured from the first side ofthe patient for a first period of time. The first patch is removed fromthe first side of the patient. A second adherent patch is placed on asecond side of the patient, in which the second adherent patch comprisessecond electrodes to measure the at least one of the electrocardiogramor the impedance. The at least one of the electrocardiogram or theimpedance is measured from the second side of the patient for a secondperiod of time after the first patch has been removed.

In many embodiments, the first side comprises at least one of a leftside or a right side of the patient, and the second side is opposite thefirst side.

In many embodiments, the second patch is removed from the second side ofthe patient, and a third adherent patch is placed on the first side ofthe patient, in which the third patch comprises third electrodes tomeasure the at least one of the electrocardiogram or the impedance. Theat least one of the electrocardiogram or the impedance is measured fromthe first side of the patient for a third period of time after thesecond patch has been removed.

In many embodiments, the third patch is removed from the first side ofthe patient. A fourth adherent patch is placed on the second side of thepatient, in which the fourth patch comprising fourth electrodes tomeasure the at least one of the electrocardiogram or the impedance. Theat least one of the electrocardiogram or the impedance is measured fromthe second side of the patient for a fourth period of time after thethird patch has been removed.

In specific embodiments, each of the first period of time, the secondperiod of time, the third period of time and the fourth period of timecomprises at least about 1 week.

In another aspect, embodiments of the present invention provide a methodof monitoring a patient for an extended period of time. A first adherentpatch is placed on a skin location on a first side of the patient, inwhich the first adherent patch comprises first electrodes to measure atleast one of an electrocardiogram or an impedance. The at least one ofthe electrocardiogram or the impedance is measured from the firstadherent patch on the first skin location for a first period of time.The first patch is removed from the first skin location. A secondadherent patch is placed on a second skin location on a second side ofthe patient, in which the second adherent patch comprises secondelectrodes to measure the at least one of the electrocardiogram or theimpedance. The at least one of the electrocardiogram or the impedance ismeasured from the second skin location for a second period of time afterthe first patch has been removed.

In many embodiments, the first skin location heals during the secondperiod of time.

In another aspect, embodiments of the present invention provide anadherent device to monitor a patient. The device comprises an adhesivepatch to adhere to a skin of the patient. At least four electrodes aremechanically coupled to the patch and capable of electrically couplingto the patient. The at least four electrodes may comprise at least twoforce electrodes and at least two sense electrodes. Impedance circuitrymay be electrically coupled to the at least two force electrodes toforce an electrical current and to the at least two sense electrodes tomeasure a hydration signal of the patient. Electrocardiogram circuitrycan be coupled to the at least two force electrodes to measure anelectrocardiogram signal of the patient.

In many embodiments, the adherent device comprises electrical switchesconnected to the at least two force electrodes to isolate the at leasttwo force electrodes from the impedance circuitry when theelectrocardiogram circuitry measures the electrocardiogram. In specificembodiments, a processor an be configured to control the impedancecircuitry and the electrocardiogram circuitry so as to time divisionmultiplex collection the hydration signal and the electrocardiogramsignal. The processor may be configured to decouple the at least twoforce electrodes from the impedance circuitry when the electrocardiogramcircuitry measures the electrocardiogram signal.

In many embodiments, the at least four electrodes comprise no more thanfour electrodes.

In some embodiments, the at least two force electrodes comprise outerelectrodes and the at least two sense electrodes comprise innerelectrodes.

In some embodiments, the at least two force electrodes comprise innerelectrodes and the at least two sense electrodes comprise outerelectrodes.

In another aspect, embodiments of the present invention provide a methodof monitoring a patient. An adhesive patch is adhered to a skin of thepatient so as to couple at least four electrodes to the skin of thepatient, in which the at least four electrodes comprise at least twoforce electrodes and at least two sense electrodes. A hydration signalof the patient is measured with impedance circuitry electrically coupledto the at least two force electrodes and to the at least two senseelectrodes, such that the at least two force electrodes force anelectrical current between the at least two force electrodes. Anelectrocardiogram signal of the patient is measured withelectrocardiogram circuitry coupled to the at least two forceelectrodes.

In many embodiments, electrical switches connected to the at least twoforce electrodes can be opened to isolate the at least two forceelectrodes from the impedance circuitry when the electrocardiogramcircuitry measures the electrocardiogram.

In many embodiments, the hydration signal and the electrocardiogramsignal can be time division multiplexed.

In another aspect, embodiments of the present inventions provide anadherent device to monitor a patient. The device comprises an adhesivepatch and at least two electrodes connected to the patch. The devicealso comprises circuitry coupled to at least two electrodes to measureat least two of an electrocardiogram signal, a respiration signal of thepatient or an activity signal of the patient, and a processor system.The adhesive patch can adhere to a skin of the patient. The electrodesare capable of electrically coupling to the patient. The processorsystem comprises a tangible medium configured to trigger an alarm inresponse to the at least two of the electrocardiogram signal, therespiration signal or the activity signal.

In many embodiments, the processor system comprises a first processorand a second processor. The first processor may comprise a tangiblemedium attached to the adherent patch. The second processor may comprisea tangible medium at a remote center.

In many embodiments, the processor system is configured to combine atleast two of the electrocardiogram signal, the respiration signal or theactivity signal, the purpose of which may be to detect an impendingcardiac decompensation. Combining may comprise at least one of adding,subtracting, multiplying, scaling, or dividing the at least two of theelectrocardiogram signal, the hydration signal, the respiration signal,or the activity signal. In some embodiments, the at least two of theelectrocardiogram signal, the respiration signal, or the activity signalcan be combined with at least one of a weighted combination, a tieredcombination, or a logic gated combination, a time weighted combinationor a rate of change.

In many embodiments, the processor system is configured to continuouslymonitor, store in tangible media, and transmit to a remote center atleast two of the electrocardiogram signal, the respiration signal or theactivity signal when the alarm is triggered.

In many embodiments, the processor system is configured to trigger thealarm and alert the patient and/or the physician in response to anadverse cardiac event.

In many embodiments, the processor system is configured to calculate andreport a patient risk of sudden cardiac death to at least one of aremote center or a physician.

In many embodiments, the processor system is configured to detect atleast one of a T-wave alternans, a pulsus alternans, an autonomicimbalance, a heart rate variability in response to at least two of theelectrocardiogram signal, the respiration signal or the activity signal.

In many embodiments, the processor system is configured to loop recordat least two of the electrocardiogram signal, the respiration signal orthe activity signal for diagnosis of an unexplained syncope and/orarrhythmia when the alarm is triggered.

In many embodiments, the processor system is configured to detect anevent comprising at least one of an atrial fibrillation in response tothe electrocardiogram signal or an acute myocardial infarction inresponse to an ST segment elevation of the electrocardiogram signal.

In many embodiments, the processor system is configured to monitor ahigh risk patient post myocardial infarction with at least two of theelectrocardiogram signal, the respiration signal or the activity signal.

In many embodiments, the processor system is configured to continuouslymonitor a bradycardia of the patient at risk for sudden death, theelectrocardiogram signal comprising at least one of a Brugada Syndromewith an ST elevation and a short QT interval or long-QT interval.

In many embodiments, the processor system is configured to monitor theelectrocardiogram signal and an alert at least one of a patient, aremote center a physician, emergency responder, or family/caregiver inresponse to an adverse event.

In many embodiments, the processor system is configured to determine atiered response to at least two of the electrocardiogram signal, therespiration signal or the activity signal.

In some embodiments, the tiered response may comprise a first tier tocontact an emergency responder in response to an immediate lifethreatening event, a second tier to contact a physician in response toan event that requires medical care, a third tier to contact a familymember and/or care giver, and a fourth tier to contact the center.

In some embodiments, the immediate life threatening event comprises atleast one of a sustained ventricular tachycardia, a sustainedventricular fibrillation, an asystole, an arrhythmia with no respirationor an arrhythmia with no patient movement.

In some embodiments, the event that requires medical care comprises anatrial fibrillation that is not immediately life threatening.

In some embodiments, the wireless communication circuitry is configuredto transmit at least two of the electrocardiogram signal, therespiration signal or the activity signal with a single wireless hopfrom the wireless communication circuitry to an intermediate device.

In another aspect, embodiments of the present invention provides amethod of monitoring a patient. An adhesive patch is adhered to a skinof the patient so as to couple at least two electrodes to the skin ofthe patient. Circuitry coupled to the at least two electrodes measuresat least two of an electrocardiogram signal of the patient, arespiration signal of the patient or an activity signal of the patient.An alarm may be triggered by a processor system in response to the atleast two of the electrocardiogram signal, the respiration signal or theactivity signal with the processor system comprising a tangible medium.

In many embodiments, the processor system comprises a first processorand a second processor. The first processor comprises a tangible mediumattached to the adherent patch and the second processor comprises atangible medium at a remote center.

In many embodiments, at least two of the electrocardiogram signal, therespiration signal, or the activity signal are combined, which may be todetect am impending cardiac decompensation. In some embodiments,combining may comprise at least one of adding, subtracting, multiplying,scaling or dividing the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signal. Insome embodiments, the at least two of the electrocardiogram signal, therespiration signal, or the activity signal can be combined with at leastone of a weighted combination, a tiered combination, or a logic gatedcombination, a time weighted combination or a rate of change.

In many embodiments, at least two of the electrocardiogram signal, therespiration signal, or the activity signal are continuously monitored,stored, and/or transmitted to a remote center.

In many embodiments, the alarm is triggered and the patient and/or thephysician is alerted in response to an adverse cardiac event.

In many embodiments, a patient risk of sudden cardiac death iscalculated and/or reported to at least one of a remote center or aphysician.

In many embodiments, at least one of a T-wave alternans, a pulsusalternans, an autonomic imbalance, a heart rate variability in responseto the at least two of the electrocardiogram signal, the respirationsignal or the activity signal is detected.

In many embodiments, the at least two of the electrocardiogram signal,the respiration signal or the activity signal is loop recorded when thealarm is triggered.

In many embodiments, an event comprising at least one of an atrialfibrillation in response to the electrocardiogram signal or an acutemyocardial infarction in response to an ST segment elevation of theelectrocardiogram signal is detected.

In many embodiments, a high risk patent post myocardial infarction ismonitored with the at least two of the electrocardiogram signal, therespiration signal or the activity signal.

In many embodiments, a bradycardia of the patient at risk for suddendeath, the electrocardiogram signal comprising at least one of a BrugadaSyndrome with an ST elevation and a short QT interval or long-QTinterval are continuously monitored.

In many embodiments, the electrocardiogram signal is monitored and/or atleast one of a patient, a remote center, a physician, emergencyresponder, or family/caregiver is alerted in response to an adverseevent.

In many embodiments, a tiered response to the at least two of theelectrocardiogram signal, the respiration signal or the activity signalis determined.

In many embodiments, the tiered response comprises a first tier tocontact an emergency responder in response to an immediate lifethreatening event, a second tier to contact a physician in response toan event that requires medical care, a third tier to contact a familymember and/or care giver, and a fourth tier to contact the center.

In many embodiments, the immediate life threatening event comprises atleast one of a sustained ventricular tachycardia, a sustainedventricular fibrillation, an asystole, an arrhythmia with no respirationor an arrhythmia with no patient movement.

In many embodiments, the event that requires medical care comprises anatrial fibrillation that is not immediately life threatening.

In some embodiments, wireless communication circuitry transmits the atleast two of the electrocardiogram signal, the respiration signal or theactivity signal with a single wireless hop from the wirelesscommunication circuitry to an intermediate device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a patient and a monitoring system comprising an adherentdevice, according to embodiments of the present invention;

FIG. 1B shows a bottom view of the adherent device as in FIG. 1Acomprising an adherent patch;

FIG. 1C shows a top view of the adherent patch, as in FIG. 1B;

FIG. 1D shows a printed circuit boards and electronic components overthe adherent patch, as in FIG. 1C;

FIG. 1D1 shows an equivalent circuit that can be used to determineoptimal frequencies for determining patient hydration, according toembodiments of the present invention;

FIG. 1E shows batteries positioned over the printed circuit board andelectronic components as in FIG. 1D;

FIG. 1F shows a top view of an electronics housing and a breathablecover over the batteries, electronic components and printed circuitboard as in FIG. 1E;

FIG. 1G shows a side view of the adherent device as in FIGS. 1A to 1F;

FIG. 1H shown a bottom isometric view of the adherent device as in FIGS.1A to 1G;

FIGS. 1I and 1J show a side cross-sectional view and an exploded view,respectively, of the adherent device as in FIGS. 1A to 1H;

FIG. 1K shows at least one electrode configured to electrically coupleto a skin of the patient through a breathable tape, according toembodiments of the present invention;

FIGS. 2A to 2C show a system to monitor a patient for an extended periodcomprising a reusable electronic component and a plurality of disposablepatch components, according to embodiments of the present invention;

FIG. 2D shows a method of using the system as in FIGS. 2A to 2C;

FIGS. 3A to 3D show a method of monitoring a patient for an extendedperiod with an adherent patch with adherent patches alternativelyadhered to the right side or the left side of the patient;

FIG. 4A shows an adherent device to measure an impedance signal and anelectrocardiogram signal, according to embodiments of the presentinvention;

FIG. 4B shows a method of measuring the impedance signal and theelectrocardiogram signal, according to embodiments of the presentinvention;

FIG. 5A shows a method for monitoring a patient and responding to asignal event; and

FIGS. 6A and 6B show clinical data measured with an adherent patchdevice.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention relate to patient monitoring.Although embodiments make specific reference to monitoring impedance andelectrocardiogram signals with an adherent patch, the system methods anddevice described herein may be applicable to any application in whichphysiological monitoring is used, for example wireless physiologicalmonitoring for extended periods.

Decompensation is failure of the heart to maintain adequate bloodcirculation. Although the heart can maintain at least some pumping ofblood, the quantity is inadequate to maintain healthy tissues. Severalsymptoms can result from decompensation including pulmonary congestion,breathlessness, faintness, cardiac palpitation, edema of theextremities, and enlargement of the liver. Cardiac decompensation canresult in slow or sudden death. Sudden Cardiac Arrest (hereinafter“SCA”), also referred to as sudden cardiac death, is an abrupt loss ofcardiac pumping function that can be caused by a ventricular arrhythmia,for example ventricular tachycardia and/or ventricular fibrillation.Although decompensation and SCA can be related in that patients withdecompensation are also at an increased risk for SCA, decompensation isprimarily a mechanical dysfunction caused by inadequate blood flow, andSCA is primarily an electrical dysfunction caused by inadequate and/orinappropriate electrical signals of the heart.

In many embodiments, the adherent devices described herein may be usedfor 90 day monitoring, or more, and may comprise completely disposablecomponents and/or reusable components, and can provide reliable dataacquisition and transfer. In many embodiments, the patch is configuredfor patient comfort, such that the adherent patch can be worn and/ortolerated by the patient for extended periods, for example 90 days ormore. The patch may be worn continuously for at least seven days, forexample 14 days, and then replaced with another patch. Adherent deviceswith comfortable patches that can be worn for extended periods and inwhich patches can be replaced and the electronics modules reused aredescribed in U.S. Pat. App. Nos. 60/972,537, entitled “Adherent Devicewith Multiple Physiological Sensors”; and 60/972,629, entitled “AdherentDevice with Multiple Physiological Sensors”, both filed on Sep. 14,2007, the full disclosures of which have been previously incorporatedherein by reference. In many embodiments, the adherent patch comprises atape, which comprises a material, preferably breathable, with anadhesive, such that trauma to the patient skin can be minimized whilethe patch is worn for the extended period. The printed circuit board maycomprise a flex printed circuit board that can flex with the patient toprovide improved patient comfort.

FIG. 1A shows a patient P and a monitoring system 10. Patient Pcomprises a midline M, a first side S1, for example a right side, and asecond side S2, for example a left side. Monitoring system 10 comprisesan adherent device 100. Adherent device 100 can be adhered to a patientP at many locations, for example thorax T of patient P. In manyembodiments, the adherent device may adhere to one side of the patient,from which side data can be collected. Work in relation with embodimentsof the present invention suggests that location on a side of the patientcan provide comfort for the patient while the device is adhered to thepatient.

Monitoring system 10 includes components to transmit data to a remotecenter 106. Remote center 106 can be located in a different buildingfrom the patient, for example in the same town as the patient, and canbe located as far from the patient as a separate continent from thepatient, for example the patient located on a first continent and theremote center located on a second continent. Adherent device 100 cancommunicate wirelessly to an intermediate device 102, for example with asingle wireless hop from the adherent device on the patient to theintermediate device. Intermediate device 102 can communicate with remotecenter 106 in many ways, for example with an internet connection and/orwith a cellular connection. In many embodiments, monitoring system 10comprises a distributed processing system with at least one processorcomprising a tangible medium of device 100, at least one processor 102Pof intermediate device 102, and at least one processor 106P at remotecenter 106, each of which processors can be in electronic communicationwith the other processors. At least one processor 102P comprises atangible medium 102T, and at least one processor 106P comprises atangible medium 106T. Remote processor 106P may comprise a backendserver located at the remote center. Remote center 106 can be incommunication with a health care provider 108A with a communicationsystem 107A, such as the Internet, an intranet, phone lines, wirelessand/or satellite phone. Health care provider 108A, for example a familymember, can be in communication with patient P with a communication, forexample with a two way communication system, as indicated by arrow 109A,for example by cell phone, email, landline. Remote center 106 can be incommunication with a health care professional, for example a physician108B, with a communication system 107B, such as the Internet, anintranet, phone lines, wireless and/or satellite phone. Physician 108Bcan be in communication with patient P with a communication, for examplewith a two way communication system, as indicated by arrow 109B, forexample by cell phone, email, landline. Remote center 106 can be incommunication with an emergency responder 108C, for example a 911operator and/or paramedic, with a communication system 107C, such as theInternet, an intranet, phone lines, wireless and/or satellite phone.Emergency responder 108C can travel to the patient as indicated by arrow109C. Thus, in many embodiments, monitoring system 10 comprises a closedloop system in which patient care can be monitored and implemented fromthe remote center in response to signals from the adherent device.

In many embodiments, the adherent device may continuously monitorphysiological parameters, communicate wirelessly with a remote center,and provide alerts when necessary. The system may comprise an adherentpatch, which attaches to the patient's thorax and contains sensingelectrodes, battery, memory, logic, and wireless communicationcapabilities. In some embodiments, the patch can communicate with theremote center, via the intermediate device in the patient's home. Insome embodiments, remote center 106 receives the patient data andapplies a patient evaluation algorithm, for example the predictionalgorithm to predict cardiac decompensation. In some embodiments, thealgorithm may comprise an algorithm to predict impending cardiacdecompensation is described in U.S. Pat. App. No. 60/972,512, the fulldisclosure of which has been previously incorporated herein byreference. When a flag is raised, the center may communicate with thepatient, hospital, nurse, and/or physician to allow for therapeuticintervention, for example to prevent decompensation.

The adherent device may be affixed and/or adhered to the body in manyways. For example, with at least one of the following an adhesive tape,a constant-force spring, suspenders around shoulders, a screw-inmicroneedle electrode, a pre-shaped electronics module to shape fabricto a thorax, a pinch onto roll of skin, or transcutaneous anchoring.Patch and/or device replacement may occur with a keyed patch (e.g.two-part patch), an outline or anatomical mark, a low-adhesive guide(place guide|remove old patch|place new patch|remove guide), or a keyedattachment for chatter reduction. The patch and/or device may comprisean adhesiveless embodiment (e.g. chest strap), and/or a low-irritationadhesive for sensitive skin. The adherent patch and/or device cancomprise many shapes, for example at least one of a dogbone, anhourglass, an oblong, a circular or an oval shape.

In many embodiments, the adherent device may comprise a reusableelectronics module with replaceable patches, and each of the replaceablepatches may include a battery. The module may collect cumulative datafor approximately 90 days and/or the entire adherent component(electronics+patch) may be disposable. In a completely disposableembodiment, a “baton” mechanism may be used for data transfer andretention, for example baton transfer may include baseline information.In some embodiments, the device may have a rechargeable module, and mayuse dual battery and/or electronics modules, wherein one module 101A canbe recharged using a charging station 103 while the other module 101B isplaced on the adherent patch with connectors. In some embodiments, theintermediate device 102 may comprise the charging module, data transfer,storage and/or transmission, such that one of the electronics modulescan be placed in the intermediate device for charging and/or datatransfer while the other electronics module is worn by the patient.

System 10 can perform the following functions: initiation, programming,measuring, storing, analyzing, communicating, predicting, anddisplaying. The adherent device may contain a subset of the followingphysiological sensors: bioimpedance, respiration, respiration ratevariability, heart rate (ave, min, max), heart rhythm, hear ratevariability (HRV), heart rate turbulence (HRT), heart sounds (e.g. S3),respiratory sounds, blood pressure, activity, posture, wake/sleep,orthopnea, temperature/heat flux, and weight. The activity sensor maycomprise one or more of the following: ball switch, accelerometer,minute ventilation, HR, bioimpedance noise, skin temperature/heat flux,BP, muscle noise, posture.

The adherent device can wirelessly communicate with remote center 106.The communication may occur directly (via a cellular or Wi-Fi network),or indirectly through intermediate device 102. Intermediate device 102may consist of multiple devices, which can communicate wired orwirelessly to relay data to remote center 106.

In many embodiments, instructions are transmitted from remote site 106to a processor supported with the adherent patch on the patient, and theprocessor supported with the patient can receive updated instructionsfor the patient treatment and/or monitoring, for example while worn bythe patient.

FIG. 1B shows a bottom view of adherent device 100 as in FIG. 1Acomprising an adherent patch 110. Adherent patch 110 comprises a firstside, or a lower side 110A, that is oriented toward the skin of thepatient when placed on the patient. In many embodiments, adherent patch110 comprises a tape 110T which is a material, preferably breathable,with an adhesive 116A. Patient side 110A comprises adhesive 116A toadhere the patch 110 and adherent device 100 to patient P. Electrodes112A, 112B, 112C and 112D are affixed to adherent patch 110. In manyembodiments, at least four electrodes are attached to the patch, forexample six electrodes. In some embodiments the patch comprises twoelectrodes, for example two electrodes to measure the electrocardiogram(ECG) of the patient. Gel 114A, gel 114B, gel 114C and gel 114D can eachbe positioned over electrodes 112A, 112B, 112C and 112D, respectively,to provide electrical conductivity between the electrodes and the skinof the patient. In many embodiments, the electrodes can be affixed tothe patch 110, for example with known methods and structures such asrivets, adhesive, stitches, etc. In many embodiments, patch 110comprises a breathable material to permit air and/or vapor to flow toand from the surface of the skin.

FIG. 1C shows a top view of the adherent patch 100, as in FIG. 1B.Adherent patch 100 comprises a second side, or upper side 110B. In manyembodiments, electrodes 112A, 112B, 112C and 112D extend from lower side110A through adherent patch 110 to upper side 110B. An adhesive 116B canbe applied to upper side 110B to adhere structures, for example abreathable cover, to the patch such that the patch can support theelectronics and other structures when the patch is adhered to thepatient. The PCB may comprise completely flex PCB, rigid PCB, rigid PCBcombined flex PCB and/or rigid PCB boards connected by cable.

FIG. 1D shows a printed circuit boards and electronic components overadherent patch 110, as in FIG. 1A to 1C. In some embodiments, a printedcircuit board (PCB), for example flex printed circuit board 120, may beconnected to electrodes 112A, 112B, 112C and 112D with connectors 122A,122B, 122C and 122D. Flex printed circuit board 120 can include traces123A, 123B, 123C and 123D that extend to connectors 122A, 122B, 122C and122D, respectively, on the flex PCB. Connectors 122A, 122B, 122C and122D can be positioned on flex printed circuit board 120 in alignmentwith electrodes 112A, 112B, 112C and 112D so as to electrically couplethe flex PCB with the electrodes. In some embodiments, connectors 122A,122B, 122C and 122D may comprise insulated wires and/or a film withconductive ink that provide strain relief between the PCB and theelectrodes. For example, connectors 122A, 122B, 122C and 122D maycomprise a flexible polyester film coated with conductive silver ink. Insome embodiments, additional PCB's, for example rigid PCB's 120A, 120B,120C and 120D, can be connected to flex printed circuit board 120.Electronic components 130 can be connected to flex printed circuit board120 and/or mounted thereon. In some embodiments, electronic components130 can be mounted on the additional PCB's.

Electronic components 130 comprise components to take physiologicmeasurements, transmit data to remote center 106 and receive commandsfrom remote center 106. In many embodiments, electronics components 130may comprise known low power circuitry, for example complementary metaloxide semiconductor (CMOS) circuitry components. Electronics components130 comprise an activity sensor and activity circuitry 134, impedancecircuitry 136 and electrocardiogram circuitry, for example ECG circuitry136. In some embodiments, electronics circuitry 130 may comprise amicrophone and microphone circuitry 142 to detect an audio signal fromwithin the patient, and the audio signal may comprise a heart soundand/or a respiratory sound, for example an S3 heart sound and arespiratory sound with rales and/or crackles.

Electronics circuitry 130 may comprise a temperature sensor, for examplea thermistor in contact with the skin of the patient, and temperaturesensor circuitry 144 to measure a temperature of the patient, forexample a temperature of the skin of the patient. A temperature sensormay be used to determine the sleep and wake state of the patient. Thetemperature of the patient can decrease as the patient goes to sleep andincrease when the patient wakes up.

Work in relation to embodiments of the present invention suggests thatskin temperature may effect impedance and/or hydration measurements, andthat skin temperature measurements may be used to correct impedanceand/or hydration measurements. In some embodiments, increase in skintemperature or heat flux can be associated with increased vaso-dilationnear the skin surface, such that measured impedance measurementdecreased, even through the hydration of the patient in deeper tissuesunder the skin remains substantially unchanged. Thus, use of thetemperature sensor can allow for correction of the hydration signals tomore accurately assess the hydration, for example extra cellularhydration, of deeper tissues of the patient, for example deeper tissuesin the thorax.

Electronics circuitry 130 may comprise a processor 146. Processor 146comprises a tangible medium, for example read only memory (ROM),electrically erasable programmable read only memory (EEPROM) and/orrandom access memory (RAM). Electronic circuitry 130 may comprise realtime clock and frequency generator circuitry 148. In some embodiments,processor 136 may comprise the frequency generator and real time clock.The processor can be configured to control a collection and transmissionof data from the impedance circuitry electrocardiogram circuitry and theaccelerometer. In many embodiments, device 100 comprise a distributedprocessor system, for example with multiple processors on device 100.

In many embodiments, electronics components 130 comprise wirelesscommunications circuitry 132 to communicate with remote center 106. Thewireless communication circuitry can be coupled to the impedancecircuitry, the electrocardiogram circuitry and the accelerometer totransmit to a remote center with a communication protocol at least oneof the hydration signal, the electrocardiogram signal or the inclinationsignal. In specific embodiments, wireless communication circuitry isconfigured to transmit the hydration signal, the electrocardiogramsignal and the inclination signal to the remote center with a singlewireless hop, for example from wireless communication circuitry 132 tointermediate device 102. The communication protocol comprises at leastone of Bluetooth, Zigbee, WiFi, WiMax, IR, amplitude modulation orfrequency modulation. In many embodiments, the communications protocolcomprises a two way protocol such that the remote center is capable ofissuing commands to control data collection.

Intermediate device 102 may comprise a data collection system to collectand store data from the wireless transmitter. The data collection systemcan be configured to communicate periodically with the remote center.The data collection system can transmit data in response to commandsfrom remote center 106 and/or in response to commands from the adherentdevice.

Activity sensor and activity circuitry 134 can comprise many knownactivity sensors and circuitry. In many embodiments, the accelerometercomprises at least one of a piezoelectric accelerometer, capacitiveaccelerometer or electromechanical accelerometer. The accelerometer maycomprises a 3-axis accelerometer to measure at least one of aninclination, a position, an orientation or acceleration of the patientin three dimensions. Work in relation to embodiments of the presentinvention suggests that three dimensional orientation of the patient andassociated positions, for example sitting, standing, lying down, can bevery useful when combined with data from other sensors, for example ECGdata and/or hydration data.

Impedance circuitry 136 can generate both hydration data and respirationdata. In many embodiments, impedance circuitry 136 is electricallyconnected to electrodes 112A, 112B, 112C and 112D in a four poleconfiguration, such that electrodes 112A and 112D comprise outerelectrodes that are driven with a current and comprise force electrodesthat force the current through the tissue. The current delivered betweenelectrodes 112A and 112D generates a measurable voltage betweenelectrodes 112B and 112C, such that electrodes 112B and 112C compriseinner, sense, electrodes that sense and/or measure the voltage inresponse to the current from the force electrodes. In some embodiments,electrodes 112B and 112C may comprise force electrodes and electrodes112A and 112B may comprise sense electrodes. The voltage measured by thesense electrodes can be used to measure the impedance of the patient anddetermine the respiration rate and/or hydration of the patient.

FIG. 1D1 shows an equivalent circuit 152 that can be used to determineoptimal frequencies for measuring patient hydration. Work in relation toembodiments of the present invention indicates that the frequency of thecurrent and/or voltage at the force electrodes can be selected so as toprovide impedance signals related to the extracellular and/orintracellular hydration of the patient tissue. Equivalent circuit 152comprises an intracellular resistance 156, or R(ICW) in series with acapacitor 154, and an extracellular resistance 158, or R(ECW).Extracellular resistance 158 is in parallel with intracellularresistance 156 and capacitor 154 related to capacitance of cellmembranes. In many embodiments, impedances can be measured and provideuseful information over a wide range of frequencies, for example fromabout 0.5 kHz to about 200 KHz. Work in relation to embodiments of thepresent invention suggests that extracellular resistance 158 can besignificantly related extracellular fluid and to cardiac decompensation,and that extracellular resistance 158 and extracellular fluid can beeffectively measured with frequencies in a range from about 0.5 kHz toabout 20 kHz, for example from about 1 kHz to about 10 kHz. In someembodiments, a single frequency can be used to determine theextracellular resistance and/or fluid. As sample frequencies increasefrom about 10 kHz to about 20 kHz, capacitance related to cell membranesdecrease the impedance, such that the intracellular fluid contributes tothe impedance and/or hydration measurements. Thus, many embodiments ofthe present invention measure hydration with frequencies from about 0.5kHz to about 20 kHz to determine patient hydration.

In many embodiments, impedance circuitry 136 can be configured todetermine respiration of the patient. In specific embodiments, theimpedance circuitry can measure the hydration at 25 Hz intervals, forexample at 25 Hz intervals using impedance measurements with a frequencyfrom about 0.5 kHz to about 20 kHz.

ECG circuitry 138 can generate electrocardiogram signals and data fromtwo or more of electrodes 112A, 112B, 112C and 112D in many ways. Insome embodiments, ECG circuitry 138 is connected to inner electrodes112B and 122C, which may comprise sense electrodes of the impedancecircuitry as described above. In some embodiments, ECG circuitry 138 canbe connected to electrodes 112A and 112D so as to increase spacing ofthe electrodes. The inner electrodes may be positioned near the outerelectrodes to increase the voltage of the ECG signal measured by ECGcircuitry 138. In many embodiments, the ECG circuitry may measure theECG signal from electrodes 112A and 112D when current is not passedthrough electrodes 112A and 112D, for example with switches as describedin U.S. App. No. 60/972,527, the full disclosure of which has beenpreviously incorporated herein by reference.

FIG. 1E shows batteries 150 positioned over the flex printed circuitboard and electronic components as in FIG. 1D. Batteries 150 maycomprise rechargeable batteries that can be removed and/or recharged. Insome embodiments, batteries 150 can be removed from the adherent patchand recharged and/or replaced.

FIG. 1F shows a top view of a cover 162 over the batteries, electroniccomponents and flex printed circuit board as in FIGS. 1A to 1E. In manyembodiments, an electronics housing 160 may be disposed under cover 162to protect the electronic components, and in some embodimentselectronics housing 160 may comprise an encapsulant over the electroniccomponents and PCB. In some embodiments, cover 162 can be adhered toadherent patch 110 with an adhesive 164 on an underside of cover 162. Inmany embodiments, electronics housing 160 may comprise a water proofmaterial, for example a sealant adhesive such as epoxy or siliconecoated over the electronics components and/or PCB. In some embodiments,electronics housing 160 may comprise metal and/or plastic. Metal orplastic may be potted with a material such as epoxy or silicone.

Cover 162 may comprise many known biocompatible cover, casing and/orhousing materials, such as elastomers, for example silicone. Theelastomer may be fenestrated to improve breathability. In someembodiments, cover 162 may comprise many known breathable materials, forexample polyester, polyamide, and/or elastane (Spandex™). The breathablefabric may be coated to make it water resistant, waterproof, and/or toaid in wicking moisture away from the patch.

FIG. 1G shows a side view of adherent device 100 as in FIGS. 1A to 1F.Adherent device 100 comprises a maximum dimension, for example a length170 from about 4 to 10 inches (from about 100 mm to about 250 mm), forexample from about 6 to 8 inches (from about 150 mm to about 200 mm). Insome embodiments, length 170 may be no more than about 6 inches (no morethan about 150 mm). Adherent device 100 comprises a thickness 172.Thickness 172 may comprise a maximum thickness along a profile of thedevice. Thickness 172 can be from about 0.2 inches to about 0.4 inches(from about 5 mm to about 10 mm), for example about 0.3 inches (about7.5 mm).

FIG. 1H shown a bottom isometric view of adherent device 100 as in FIGS.1A to 1G. Adherent device 100 comprises a width 174, for example amaximum width along a width profile of adherent device 100. Width 174can be from about 2 to about 4 inches (from about 50 mm to 100 mm), forexample about 3 inches (about 75 mm).

FIGS. 1I and 1J show a side cross-sectional view and an exploded view,respectively, of adherent device 100 as in FIGS. 1A to 1H. Device 100comprises several layers. Gel 114A, or gel layer, is positioned onelectrode 112A to provide electrical conductivity between the electrodeand the skin. Electrode 112A may comprise an electrode layer. Adherentpatch 110 may comprise a layer of breathable tape 110T, for example aknown breathable tape, such as tricot-knit polyester fabric. An adhesive116A, for example a layer of acrylate pressure sensitive adhesive, canbe disposed on underside 110A of adherent patch 110.

A gel cover 180, or gel cover layer, for example a polyurethanenon-woven tape, can be positioned over patch 110 comprising thebreathable tape. A PCB layer, for example flex printed circuit board120, or flex PCB layer, can be positioned over gel cover 180 withelectronic components 130 connected and/or mounted to flex printedcircuit board 120, for example mounted on flex PCB so as to comprise anelectronics layer disposed on the flex PCB layer. In many embodiments,the adherent device may comprise a segmented inner component, forexample the PCB may be segmented to provide at least some flexibility.In many embodiments, the electronics layer may be encapsulated inelectronics housing 160 which may comprise a waterproof material, forexample silicone or epoxy. In many embodiments, the electrodes areconnected to the PCB with a flex connection, for example trace 123A offlex printed circuit board 120, so as to provide strain relive betweenthe electrodes 112A, 112B, 112C and 112D and the PCB.

Gel cover 180 can inhibit flow of gel 114A and liquid. In manyembodiments, gel cover 180 can inhibit gel 114A from seeping throughbreathable tape 110T to maintain gel integrity over time. Gel cover 180can also keep external moisture, for example liquid water, frompenetrating though the gel cover into gel 114A while allowing moisturevapor from the gel, for example moisture vapor from the skin, totransmit through the gel cover.

In many embodiments, cover 162 can encase the flex PCB and/orelectronics and can be adhered to at least one of the electronics, theflex PCB or adherent patch 110, so as to protect at least theelectronics components and the PCB. Cover 162 can attach to adherentpatch 110 with adhesive 116B. Cover 162 can comprise many knownbiocompatible cover materials, for example silicone. Cover 162 cancomprise an outer polymer cover to provide smooth contour withoutlimiting flexibility. In many embodiments, cover 162 may comprise abreathable fabric. Cover 162 may comprise many known breathable fabrics,for example breathable fabrics as described above. In some embodiments,the breathable cover may comprise a breathable water resistant cover. Insome embodiments, the breathable fabric may comprise polyester, nylon,polyamide, and/or elastane (Spandex™) to allow the breathable fabric tostretch with body movement. In some embodiments, the breathable tape maycontain and elute a pharmaceutical agent, such as an antibiotic,anti-inflammatory or antifungal agent, when the adherent device isplaced on the patient.

The breathable cover 162 and adherent patch 110 comprise breathable tapecan be configured to couple continuously for at least one week the atleast one electrode to the skin so as to measure breathing of thepatient. The breathable tape may comprise the stretchable breathablematerial with the adhesive and the breathable cover may comprises astretchable water resistant material connected to the breathable tape,as described above, such that both the adherent patch and cover canstretch with the skin of the patient. Arrows 182 show stretching ofadherent patch 110, and the stretching of adherent patch can be at leasttwo dimensional along the surface of the skin of the patient. As notedabove, connectors 122A, 122B, 122C and 122D between PCB 130 andelectrodes 112A, 112B, 112C and 112D may comprise insulated wires thatprovide strain relief between the PCB and the electrodes, such that theelectrodes can move with the adherent patch as the adherent patchcomprising breathable tape stretches. Arrows 184 show stretching ofcover 162, and the stretching of the cover can be at least twodimensional along the surface of the skin of the patient. Cover 162 canbe attached to adherent patch 110 with adhesive 116B such that cover 162stretches and/or retracts when adherent patch 110 stretches and/orretracts with the skin of the patient. For example, cover 162 andadherent patch 110 can stretch in two dimensions along length 170 andwidth 174 with the skin of the patient, and stretching along length 170can increase spacing between electrodes. Stretching of the cover andadherent patch 110, for example in two dimensions, can extend the timethe patch is adhered to the skin as the patch can move with the skinsuch that the patch remains adhered to the skin. Electronics housing 160can be smooth and allow breathable cover 162 to slide over electronicshousing 160, such that motion and/or stretching of cover 162 is slidablycoupled with housing 160. The printed circuit board can be slidablycoupled with adherent patch 110 that comprises breathable tape 110T,such that the breathable tape can stretch with the skin of the patientwhen the breathable tape is adhered to the skin of the patient, forexample along two dimensions comprising length 170 and width 174.Electronics components 130 can be affixed to printed circuit board 120,for example with solder, and the electronics housing can be affixed overthe PCB and electronics components, for example with dip coating, suchthat electronics components 130, printed circuit board 120 andelectronics housing 160 are coupled together. Electronics components130, printed circuit board 120, and electronics housing 160 are disposedbetween the stretchable breathable material of adherent patch 110 andthe stretchable water resistant material of cover 160 so as to allow theadherent patch 110 and cover 160 to stretch together while electronicscomponents 130, printed circuit board 120, and electronics housing 160do not stretch substantially, if at all. This decoupling of electronicshousing 160, printed circuit board 120 and electronic components 130 canallow the adherent patch 110 comprising breathable tape to move with theskin of the patient, such that the adherent patch can remain adhered tothe skin for an extended time of at least one week, for example two ormore weeks.

An air gap 169 may extend from adherent patch 110 to the electronicsmodule and/or PCB, so as to provide patient comfort. Air gap 169 allowsadherent patch 110 and breathable tape 110T to remain supple and move,for example bend, with the skin of the patient with minimal flexingand/or bending of printed circuit board 120 and electronic components130, as indicated by arrows 186. Printed circuit board 120 andelectronics components 130 that are separated from the breathable tape110T with air gap 169 can allow the skin to release moisture as watervapor through the breathable tape, gel cover, and breathable cover. Thisrelease of moisture from the skin through the air gap can minimize, andeven avoid, excess moisture, for example when the patient sweats and/orshowers.

The breathable tape of adherent patch 110 may comprise a first mesh witha first porosity and gel cover 180 may comprise a breathable tape with asecond porosity, in which the second porosity is less than the firstporosity to minimize, and even inhibit, flow of the gel through thebreathable tape. The gel cover may comprise a polyurethane film with thesecond porosity.

In many embodiments, the adherent device comprises a patch component andat least one electronics module. The patch component may compriseadherent patch 110 comprising the breathable tape with adhesive coating116A, at least one electrode, for example electrode 114A and gel 114.The at least one electronics module can be separable from the patchcomponent. In many embodiments, the at least one electronics modulecomprises the flex printed circuit board 120, electronic components 130,electronics housing 160 and cover 162, such that the flex printedcircuit board, electronic components, electronics housing and cover arereusable and/or removable for recharging and data transfer, for exampleas described above. In many embodiments, adhesive 116B is coated onupper side 110A of adherent patch 110B, such that the electronics modulecan be adhered to and/or separated from the adhesive component. Inspecific embodiments, the electronic module can be adhered to the patchcomponent with a releasable connection, for example with Velcro™, aknown hook and loop connection, and/or snap directly to the electrodes.Two electronics modules can be provided, such that one electronicsmodule can be worn by the patient while the other is charged, asdescribed above. Monitoring with multiple adherent patches for anextended period is described in U.S. Pat. App. No. 60/972,537, the fulldisclosure of which has been previously incorporated herein byreference. Many patch components can be provided for monitoring over theextended period. For example, about 12 patches can be used to monitorthe patient for at least 90 days with at least one electronics module,for example with two reusable electronics modules.

At least one electrode 112A can extend through at least one aperture180A in the breathable tape 110 and gel cover 180.

In some embodiments, the adhesive patch may comprise a medicated patchthat releases a medicament, such as antibiotic, beta-blocker, ACEinhibitor, diuretic, or steroid to reduce skin irritation. The adhesivepatch may comprise a thin, flexible, breathable patch with a polymergrid for stiffening. This grid may be anisotropic, may use electroniccomponents to act as a stiffener, may use electronics-enhanced adhesiveelution, and may use an alternating elution of adhesive and steroid.

FIG. 1K shows at least one electrode 190 configured to electricallycouple to a skin of the patient through a breathable tape 192. In manyembodiments, at least one electrode 190 and breathable tape 192 compriseelectrodes and materials similar to those described above. Electrode 190and breathable tape 192 can be incorporated into adherent devices asdescribed above, so as to provide electrical coupling between the skinan electrode through the breathable tape, for example with the gel.

FIGS. 2A to 2C show a schematic illustration of a system 200 to monitora patient for an extended period. FIG. 2A shows a schematic illustrationof system 200 comprising a reusable electronics module 210 and aplurality of disposable patch components comprising a first disposablepatch component 220A, a second disposable patch component 220B, a thirddisposable patch component 220C and a fourth disposable patch component220D. Although four patch components a shown the plurality may compriseas few as two patch component and as many as three or more patchcomponents, for example 25 patch components.

FIG. 2B shows a schematic illustration of a side cross-sectional view ofreusable electronics module 210. Reusable electronics module 210 maycomprises many of the structures described above that may comprise theelectronics module. In many embodiments, reusable electronics module 210comprises a PCB, for example a flex PCB 212, electronics components 216,batteries 216, and a cover 217, for example as described above. In someembodiments, reusable electronics module 210 may comprise an electronicshousing over the electronics components and/or PCB as described above.The electronics components may comprise circuitry and/or sensors formeasuring ECG signals, hydration impedance signals, respirationimpedance signals and accelerometer signals, for example as describedabove. In many embodiments, reusable electronics module 210 comprises aconnector 219 adapted to connect to each of the disposable patchcomponents, sequentially, for example one disposable patch component ata time. Connector 219 can be formed in many ways, and may comprise knownconnectors as described above, for example a snap. In some embodiments,the connectors on the electronics module and adhesive component can bedisposed at several locations on the reusable electronics module anddisposable patch component, for example near each electrode, such thateach electrode can couple directly to a corresponding location on theflex PCB of the reusable electronics component.

Alternatively or in combination with batteries 216, each of theplurality of disposable patch components may comprise a disposablebattery. For example first disposable patch component 220A may comprisea disposable battery 214A; second disposable patch component 220B maycomprise a disposable battery 214B; third disposable patch component220C may comprise a disposable battery 214C; and a fourth disposablepatch component 220D may comprise a disposable battery 214D. Each of thedisposable batteries, 214A, 214B, 214C and 214D may be affixed to eachof disposable patches 220A, 220B, 220C and 220D, respectively, such thatthe batteries are adhered to the disposable patch component before,during and after the respective patch component is adhered to thepatient. Each of the disposable batteries, 214A, 214B, 214C and 214D maybe coupled to connectors 215A, 215B, 215C and 215D, respectively. Eachof connectors 215A, 215B, 215C and 215D can be configured to couple to aconnector of the reusable module 220, so as to power the reusable modulewith the disposable battery coupled thereto. Each of the disposablebatteries, 214A, 214B, 214C and 214D may be coupled to connectors 215A,215B, 215C and 215D, respectively, such that the batteries are notcoupled to the electrodes of the respective patch component, so as tominimize, and even avoid, degradation of the electrodes and/or gelduring storage when each disposable battery is adhered to eachrespective disposable patch component.

FIG. 2C shows a schematic illustration first disposable patch component220A of the plurality of disposable patch components that is similar tothe other disposable patch components, for example second disposablepatch component 220B, third disposable patch component 220C and fourthdisposable patch component 220C. The disposable patch componentcomprises a breathable tape 227A, an adhesive 226A on an underside ofbreathable tape 227A to adhere to the skin of the patient, and at leastfour electrodes 222A. The at least four electrodes 224A are configuredto couple to the skin of a patient, for example with a gel 226A, in someembodiments the electrodes may extend through the breathable tape tocouple directly to the skin of the patient with aid form the gel. Insome embodiments, the at least four electrodes may be indirectly coupledto the skin through a gel and/or the breathable tape, for example asdescribed above. A connector 229A on the upper side of the disposableadhesive component can be configured for attachment to connector 219 onreusable electronics module 210 so as to electrically couple theelectrodes with the electronics module. The upper side of the disposablepatch component may comprise an adhesive 224A to connect the disposablepatch component to the reusable electronics module. The reusableelectronics module can be adhered to the patch component with manyadditional known ways to adhere components, for example with Velcro™comprising hooks and loops, snaps, a snap fit, a lock and keymechanisms, magnets, detents and the like.

FIG. 2D shows a method 250 of using system 200, as in FIGS. 2A to 2C. Astep 252 adheres electronics module 210 to first disposable adherentpatch component 220A of the plurality of adherent patch components andadheres the first disposable patch component to the skin of the patient,for example with the first adherent patch component adhered to thereusable electronics module. A step 254 removes the first disposableadherent patch from the patient and separates first disposable adherentpatch component 220A from reusable electronics module 210. A step 256adheres electronics module 210 to second disposable adherent patchcomponent 220B and adheres the second disposable patch component to theskin of the patient, for example with the second adherent patchcomponent adhered to the reusable electronics module. A step 258 removesthe second disposable adherent patch from the patient and separatessecond disposable adherent patch component 220B from reusableelectronics module 210. A step 260 adheres electronics module 210 tothird disposable adherent patch component 220C and adheres the thirddisposable patch component to the skin of the patient, for example withthe third adherent patch component adhered to the reusable electronicsmodule. A step 262 removes the third disposable adherent patch from thepatient and separates third disposable adherent patch component 220Cfrom reusable electronics module 210. A step 264 adheres electronicsmodule 210 to fourth disposable adherent patch component 220D andadheres the fourth disposable patch component to the skin of thepatient, for example with the third adherent patch component adhered tothe reusable electronics module. A step 268 removes the fourthdisposable adherent patch from the patient and separates fourthdisposable adherent patch component 220D from reusable electronicsmodule 210.

In many embodiments, physiologic signals, for example ECG, hydrationimpedance, respiration impedance and accelerometer impedance aremeasured when the adherent patch component is adhered to the patient,for example when any of the first, second, third or fourth disposableadherent patches is adhered to the patient.

FIGS. 3A to 3D show a method 300 of monitoring a patient for an extendedperiod with adherent patches alternatively adhered to a right side 302and a left side 304 of the patient. Work in relation to embodiments ofthe present invention suggests that repeated positioning of a patch atthe same location can irritate the skin and may cause patientdiscomfort. This can be avoided by alternating the patch placementbetween left and right sides of the patient, often a front left and afront right side of the patient where the patient can reach easily toreplace the patch. In some embodiments, the patch location can bealternated on the same side of the patient, for example higher and/orlower on the same side of the patient without substantial overlap toallow the skin to recover and/or heal. In many embodiments, the patchcan be symmetrically positioned on an opposite side such that signalsmay be similar to a previous position of the patch symmetricallydisposed on an opposite side of the patient. In many embodiments, theduration between removal of one patch and placement of the other patchcan be short, such that any differences between the signals may beassumed to be related to placement of the patch, and these differencescan be removed with signal processing.

In many embodiments each patch comprises at least four electrodesconfigured to measure an ECG signal and impedance, for example hydrationand/or respiration impedance. In many embodiments, the patient comprisesa midline 306, with first side, for example right side 302, and secondside, for example left side 304, symmetrically disposed about themidline. A step 310 adheres a first adherent patch 312 to at a firstlocation 314 on a first side 302 of the patient for a first period oftime, for example about 1 week. While the adherent patch 312 is positionat first location 314 on the first side of the patient, the electrodesof the patch are coupled to the skin of the patient to measure the ECGsignal and impedance signals.

A step 320 removes patch 312 and adheres a second adherent patch 322 ata second location 324 on a second side 206 of the patient for a secondperiod of time, for example about 1 week. In many embodiments, secondlocation 324 can be symmetrically disposed opposite first location 314across midline 304, for example so as to minimize changes in thesequential impedance signals measured from the second side and firstside. While adherent patch 322 is position at second location 324 on thesecond side of the patient, the electrodes of the patch are coupled tothe skin of the patient to measure the ECG signal and impedance signals.In many embodiments, while adherent patch 322 is positioned at secondlocation 324, skin at first location 314 can heal and recover fromadherent coverage of the first patch. In many embodiments, secondlocation 324 is symmetrically disposed opposite first location 314across midline 304, for example so as to minimize changes in theimpedance signals measured between the first side and second side. Inmany embodiments, the duration between removal of one patch andplacement of the other patch can be short, such that any differencesbetween the signals may be assumed to be related to placement of thepatch, and these differences can be removed with signal processing.

A step 330 removes second patch 322 and adheres a third adherent patch332 at a third location 334 on the first side, for example right side302, of the patient for a third period of time, for example about 1week. In many embodiments, third location 334 can be symmetricallydisposed opposite second location 324 across midline 304, for example soas to minimize changes in the sequential impedance signals measured fromthe third side and second side. In many embodiments, third location 334substantially overlaps with first location 314, so as to minimizedifferences in measurements between the first adherent patch and thirdadherent patch that may be due to patch location. While adherent patch332 is positioned at third location 334 on the first side of thepatient, the electrodes of the patch are coupled to the skin of thepatient to measure the ECG signal and impedance signals. In manyembodiments, while adherent patch 332 is positioned at third location334, skin at second location 324 can heal and recover from adherentcoverage of the second patch. In many embodiments, the duration betweenremoval of one patch and placement of the other patch can be short, suchthat any differences between the signals may be assumed to be related toplacement of the patch, and these differences can be removed with signalprocessing.

A step 340 removes third patch 332 and adheres a fourth adherent patch342 at a fourth location 344 on the second side, for example left side306, of the patient for a fourth period of time, for example about 1week. In many embodiments, fourth location 344 can be symmetricallydisposed opposite third location 334 across midline 304, for example soas to minimize changes in the sequential impedance signal measured fromthe fourth side and third side. In many embodiments, fourth location 344substantially overlaps with second location 324, so as to minimizedifferences in measurements between the second adherent patch and fourthadherent patch that may be due to patch location. While adherent patch342 is positioned at fourth location 344 on the second side of thepatient, the electrodes of the patch are coupled to the skin of thepatient to measure the ECG signal and impedance signals. In manyembodiments, while adherent patch 342 is positioned at fourth location324, skin at third location 334 can heal and recover from adherentcoverage of the third patch. In many embodiments, the duration betweenremoval of one patch and placement of the other patch can be short, suchthat any differences between the signals may be assumed to be related toplacement of the patch, and these differences can be removed with signalprocessing.

It should be appreciated that the specific steps illustrated in FIGS. 3Ato 3D provide a particular method of monitoring a patient for anextended period, according to an embodiment of the present invention.Other sequences of steps may also be performed according to alternativeembodiments. For example, alternative embodiments of the presentinvention may perform the steps outlined above in a different order.Moreover, the individual steps illustrated in FIGS. 3A to 3D may includemultiple sub-steps that may be performed in various sequences asappropriate to the individual step. Furthermore, additional steps may beadded or removed depending on the particular applications. One ofordinary skill in the art would recognize many variations,modifications, and alternatives.

FIG. 4A shows a monitoring system 400 comprising an adherent device 410to measure an impedance signal and an electrocardiogram signal. Device410 may comprise wireless communication circuitry, accelerometer sensorsand/or circuitry and many sensors and electronics components andstructures as described above. Adherent device 410 comprises at leastfour electrodes. In many embodiments, the at least four electrodescomprises four electrodes, for example a first electrode 412A, a secondelectrode 412B, a third electrode 412C and a fourth electrode 412D. Workin relation to embodiments of the present invention suggests thatembodiments in which the at least four electrodes comprises fourelectrodes can decrease a footprint, or size, of the device on thepatient and may provide improved patient comfort. In many embodiments,first electrode 412A and fourth electrode 412D comprise outerelectrodes, and second electrode 412B and third electrode 412C compriseinner electrodes, for example in embodiments where the electrodes arearranged in an elongate pattern.

Adherent device 410 comprises impedance circuitry 420 that can be usedto measure hydration and respiration of the patient, and ECG circuitry430 that is used to measure an electrocardiogram signal of the patient.Impedance circuitry 420 comprises force circuitry connected to the outerelectrodes to drive a current between the electrodes. Impedancecircuitry 420 comprises sense circuitry to measure a voltage between theinner electrodes resulting from the current passed between the outerforce electrodes, such that the impedance of the tissue can bedetermined. Impedance circuitry 420 may comprise known 4-pole, orquadrature, low power circuitry. ECG circuitry 430 can be connected tothe outer electrodes, or force electrodes, to measure an ECG signal.Work in relation to embodiments of the present invention suggests thatthis use of the outer electrodes can increase the ECG signal as comparedto the inner electrodes, in some embodiments, that may be due to theincreased distance between the outer electrodes. ECG circuitry 430 maycomprise known ECG circuitry and components, for example low powerinstrumentation and/or operational amplifiers.

In many embodiments, electronic switch 432A and electronic switch 432Dare connected in series between impedance circuitry 420 and electrode412A and 412D, respectively. In many embodiments, electronic switch 432Aand electronic switch 432D open such that the outer electrodes can beisolated from the impedance circuitry when the ECG circuitry measuresECG signals. When electronic switch 432A and electronic switch 432D areclosed, impedance circuitry 420 can force electrical current through theouter electrodes to measure impedance. In many embodiments, electronicswitch 432A and electronic switch 432D can be located in the samepackaging, and may comprise CMOS, precision, analog switches with lowpower consumption, low leakage currents, and fast switching speeds.

A processor 440 can be connected to electronic switch 423A, electronicswitch 432D, impedance circuitry 420 and ECG circuitry 430 to controlmeasurement of the ECG and impedance signals. Processor 430 comprises atangible medium, for example read only memory (ROM), electricallyerasable programmable read only memory (EEPROM) and/or random accessmemory (RAM). In many embodiments, processor 440 controls themeasurements such that the measurements from impedance circuitry 420 andECG circuitry 430 are time division multiplexed in response to controlsignals from processor 440.

FIG. 4B shows a method 450 of measuring the impedance signal and theelectrocardiogram signal with processor 440. A step 452 closes theswitches. A step 454 drives the force electrodes. A step 456 measuresthe impedance signal with the inner electrodes. A step 458 determinesthe impedance, hydration and/or respiration from the impedance signal. Astep 460 opens the switches. A step 462 measures the ECG signal with theouter electrodes. A step 464 stores the data from the impedance signalsand ECG signals. A step 466 processes the data. A step 468 transmits thedata, for example wirelessly to the remove center. A step 470 repeatsthe above steps.

It should be appreciated that the specific steps illustrated in FIG. 4Bprovide a particular method of measuring signals, according to anembodiment of the present invention. Other sequences of steps may alsobe performed according to alternative embodiments. For example,alternative embodiments of the present invention may perform the stepsoutlined above in a different order. Moreover, the individual stepsillustrated in FIG. 4B may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

FIG. 5A shows a method 500 for monitoring a patient and responding to asignal event. A step 501 activates a processor system. A step 503calculates a risk of sudden cardiac death. A step 506 reports to aremote center and/or physician. A step 509 combines at least two of theelectrocardiogram signal, respiration signal, and/or activity signals. Astep 512 detects an adverse cardiac event. An adverse cardiac event maycomprise an atrial fibrillation in response to the electrocardiogramsignal and/or an acute myocardial infarction in response to an STsegment elevation of the electrocardiogram signal. A step 515 triggersan alarm. A step 518 continuously monitors and stores in tangible mediaat least two of the electrocardiogram signal, the respiration signal, orthe activity signal. In some embodiments, a step may also comprisemonitoring a high risk patent post myocardial infarction with the atleast two of the electrocardiogram signal, the respiration signal or theactivity signal, and/or a bradycardia of the patient at risk for suddendeath. The electrocardiogram signal may comprise at least one of aBrugada Syndrome with an ST elevation and a short QT interval or long-QTinterval. A step 521 loop records the aforementioned data. A step 524determines a tiered response. In many embodiments, the tiered responsemay comprise tiers, or levels, appropriate to the detected status of thepatient. A step 527 comprises a first tier response which alerts anemergency responder. A step 530 comprises a second tier response whichalerts a physician. A step 533 comprises a third tier response whichalerts a patient, family, or caregiver. A step 537 comprises a fourthtier response which alerts a remote center. A tiered response may alsocomprise of wirelessly transmitting the at least two of the electrocardiogram signal, the respiration signal, or the activity signal with asingle wireless hop from a wireless communication circuitry to anintermediate device.

The signals can be combined in many ways. In some embodiments, thesignals can be used simultaneously to determine the impending cardiacdecompensation.

In some embodiments, the signals can be combined by using the at leasttwo of the electrocardiogram signal, the respiration signal or theactivity signal to look up a value in a previously existing array.

TABLE 1 Lookup Table for ECG and Respiration Signals. HeartRate/Respiration A-B bpm C-D bpm E-F bpm U-V per min N N Y W-X per min NY Y Y-Z per min Y Y Y

Table 1 shows combination of the electrocardiogram signal with therespiration signal to look up a value in a pre-existing array. Forexample, at a heart rate in the range from A to B bpm and a respirationrate in the range from U to V per minute triggers a response of N. Insome embodiments, the values in the table may comprise a tier or levelof the response, for example four tiers. In specific embodiments, thevalues of the look up table can be determined in response to empiricaldata measured for a patient population of at least about 100 patients,for example measurements on about 1000 to 10,000 patients. The look uptable shown in Table 1 illustrates the use of a look up table accordingto one embodiment, and one will recognize that many variables can becombined with a look up table.

In some embodiments, the table may comprise a three or more dimensionallook up table, and the look up table may comprises a tier, or level, ofthe response, for example an alarm.

In some embodiments, the signals may be combined with at least one ofadding, subtracting, multiplying, scaling or dividing the at least twoof the electrocardiogram signal, the respiration signal or the activitysignal. In specific embodiments, the measurement signals can be combinedwith positive and or negative coefficients determined in response toempirical data measured for a patient population of at least about 100patients, for example data on about 1000 to 10,000 patients.

In some embodiments, a weighted combination may combine at least twomeasurement signals to generate an output value according to a formulaof the general form

OUTPUT=aX+bY

where a and b comprise positive or negative coefficients determined fromempirical data and X, and Z comprise measured signals for the patient,for example at least two of the electrocardiogram signal, therespiration signal or the activity signal. While two coefficients andtwo variables are shown, the data may be combined with multiplicationand/or division. One or more of the variables may be the inverse of ameasured variable.

In some embodiments, the ECG signal comprises a heart rate signal thatcan be divided by the activity signal. Work in relation to embodimentsof the present invention suggest that an increase in heart rate with adecrease in activity can indicate an impending decompensation. Thesignals can be combined to generate an output value with an equation ofthe general form

OUTPUT=aX/Y+bZ

where X comprise a heart rate signal, Y comprises an activity signal andZ comprises a respiration signal, with each of the coefficientsdetermined in response to empirical data as described above.

In some embodiments, the data may be combined with a tiered combination.While many tiered combinations can be used a tiered combination withthree measurement signals can be expressed as

OUTPUT=(ΔX)+(ΔY)+(ΔZ)

where (ΔX), (ΔY), (ΔZ) may comprise change in heart rate signal frombaseline, change in respiration signal from baseline and change inactivity signal from baseline, and each may have a value of zero or one,based on the values of the signals. For example if the heart rateincrease by 10%, (ΔX) can be assigned a value of 1. If respirationincreases by 5%, (ΔY) can be assigned a value of 1. If activitydecreases below 10% of a baseline value (ΔZ) can be assigned a valueof 1. When the output signal is three, a flag may be set to trigger analarm.

In some embodiments, the data may be combined with a logic gatedcombination. While many logic gated combinations can be used, a logicgated combination with three measurement signals can be expressed as

OUTPUT=(ΔX)AND(ΔY)AND(ΔZ)

where (ΔX), (ΔY), (ΔZ) may comprise change in heart rate signal frombaseline, change in respiration signal from baseline and change inactivity signal from baseline, and each may have a value of zero or one,based on the values of the signals. For example if the heart rateincrease by 10%, (ΔX) can be assigned a value of 1. If respirationincreases by 5%, (ΔY) can be assigned a value of 1. If activitydecreases below 10% of a baseline value (ΔZ) can be assigned a valueof 1. When each of (ΔX), (ΔY), (ΔZ) is one, the output signal is one,and a flag may be set to trigger an alarm. If any one of (ΔX), (ΔY) or(ΔZ) is zero, the output signal is zero and a flag may be set so as notto trigger an alarm. While a specific example with AND gates has beenshown the data can be combined in may ways with known gates for exampleNAND, NOR, OR, NOT, XOR, XNOR gates. In some embodiments, the gatedlogic may be embodied in a truth table.

The processor system, as described above, performs the methods 500,including many of the steps described above. It should be appreciatedthat the specific steps illustrated in FIG. 5A provide a particularmethod of monitoring a patient and responding to a signal event,according to an embodiment of the present invention. Other sequences ofsteps may also be performed according to alternative embodiments. Forexample, alternative embodiments of the present invention may performthe steps outlined above in a different order. Moreover, the individualsteps illustrated in FIG. 5A may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

Experimental Clinical Study

The protocol below has been used to measure signals from actual patientswith an adherent device. These data show that an adherent patch asdescribed above can be continuously adhered for at least one week. Thesedata also show that 90 day continuous in home monitoring can be achievedwith a set of 13 patches in which one of the patches is replaced eachweek. The clinical testing device used an adherent device withmodifications, as described more fully below and referred to as the MSsystem (multi-sensor). Although the clinical device did not includewireless circuitry and processor circuitry supported with the patchadhered to the skin of the patient, these data do show that such adevice, as described above, can be made by one of ordinary skill in theart based on the teachings described herein. Additional empiricalstudies can be conducted on a suitable number of patients.

MS Clinical System Description

The MS clinical system includes many of the structure componentsdescribed above. There is a flexible connection between the electrodesand the flex PCB, for example wires or polyurethane with silver ink. Thecover can stretch with the breathable tape on both the clinical deviceand the above described wireless device. There is generally a gapbetween the flex PCB and breathable tape in both clinical and abovedescribed wireless devices. The tested device used weights to at leastpartially simulate the weight of wireless and processor circuitry. Theadherent device of the MS clinical system comprises four electrodes tomeasure bioimpedance and ECG signals and a 3-axis accelerometer, asdescribed above. Bioimpedance signals were used to determine patientrespiration and patient hydration, and accelerometer signals were usedto determine patient activity and posture. The MS clinical adherentpatch device comprising the sensors and at least some sensor circuitrywere connected to a processor to record data. The processor wasconnected to the tested adherent device with wires and supported awayfrom the tested adherent patch device, for example around the patient'swaist. Data were collected at regular intervals and uploaded to a remotesite, as described above.

Clinical testing of the MS clinical system shows the effectiveness ofthe structures for continuous adherence of at least one week and datacollection, and that patches can be successively removed and replaced bythe patient for in-home monitoring. This effectiveness has been shownwithout requiring fully functional electronics circuitry such as abattery, wireless circuitry and process circuitry on the adherentdevice. For example, the MS system includes an insert with about 20 g ofadditional weight. Although an insert with a 20 gram weight was used forthe MS clinical device, greater amounts of weight and circuitry can beused, for example about 30-50 g. The patch device may be modified toaccommodate additional weight, for example by increasing the size of theadherent surface. The shape of the MS clinical patch is generallyelongate, similar to the elongate shape shown above.

Study Design and Rationale

The MS System is used in a clinical study of heart failure patients togather data that can be used to develop an algorithm for diagnosing andpredicting impending heart failure decompensation events. Eventstypically manifest as heart failure-related hospitalization, emergencyroom or urgent care visits leading to a change in oral or IV diuretictreatment.

The purpose of the clinical study is to correlate physiological signalsrecorded by the system to clinical events of acute heart failuredecompensation (AHFD). Signals from the patch can be weighted andcombined to determine an index that associates physiologic parameters toimpending events of decompensation. Patients who have been classified asNew York Heart Association class III and IV within the last 12 monthsand have had a recent AHFD event can be enrolled into the study and aremonitored with the MS system for approximately 90 days.

AHFD events are defined as any of the following:

1) Any heart failure related ER, Urgent Care, in-office visit orhospitalization requiring administration of IV diuretics, administrationof IV inotropes, or ultrafiltration for fluid removal.

2) A change in diuretic, defined as a change in diuretic directed by thehealth care provider occurring inside a hospital, emergency room, orurgent care setting (i.e. no patient self-directed changes tomedications not approved by a health care provider would be included),that satisfies one or more of the following: a) a change in the type ofdiuretic the patient is taking, b) a dose increase of an existingdiuretic, or c) the addition of another diuretic.

3) A heart failure decompensation event for which death is the outcome.

Patients enrolled in the study were asked to replace the patch weekly.The study can enroll at least about 550 patients. The patient wasprovided with a kit comprising 13 patches for replacement. The patcheswere placed on alternating left and right sides of the patient's thorax,as described above, to minimize progressive irritation.

The data collected in the study can be used to develop an algorithm toat least one of detect, diagnose or predict an impending cardiacdecompensation. The algorithm can be implemented on a processor systemas described above. Known methods can be used to analyze the data, forexample splitting the patients into two groups, one to developparameters for the algorithm and a second group to test the algorithmdeveloped with the first group. In many embodiments, the signal of thealgorithm may comprise a simple binary output for impending cardiacdecompensation of the patient. The logic output, yes or no, can bedetermined in response to patient data combined as described above. Thelogic output may comprise a signal, such as a binary Y or N signal.

The developed algorithm can be evaluated with composite sensitivity andfalse positive patient signal status rates. The sensitivity may bedefined as the percent of true positive events out of all conditionpresent events, and the false positive patient status signal status ratecan be defined as the number of false positive patient status signalsper patient-years of follow up. For example, the sensitivity can be atleast 50%, for example at least 60%, at least 70%, or even at least 80%.The false positive patient signal status rate may be limited to no morethan about 1.1 false positive patient status signals per patient year,for example no more than about 1.0 false positive patient status signalsper patient year, no more than about 0.9 false positive patient statussignals per patient year, and even no more than about 0.8 false positivepatient status signals per patient year.

Clinical Results

Clinical data are available for the first 180 patients enrolled in thestudy.

FIGS. 6A and 6B show clinical data measured with an adherent patchdevice, in accordance with the above protocol. FIG. 6A shows data from apatient with the MS patch adhered to a first patient, and the data wasacquired over the 90 day period with the series of 13 patches. Thesignals measured included Heart Rate (beats per minute), Heart RateVariability (ms), Respiratory Rate (breaths per minute), Activity(m-G's) and Body Fluid (Ohms). FIG. 6B shows data from a second patientsimilar to FIG. 6A.

Of the 180 patients who have completed the study with the MS adherentpatch, as described above, all patches in all patients adheredcontinuously without patch failure. In all patients, the first patchadhered continuously for the first week. With the exception of a handfulof patient deaths and early withdrawals that were unrelated to devicefailure, all patients reached the end of 90-day follow-up period havingused 13 weekly patches without incident. None of the 180 patients showedskin irritation or damage that required withdrawal from the study.

The above data show that the wireless adherent patch device can beconstructed for in home wireless patient monitoring for an extendedperiod of at least 90 day, in which each patch of a set is continuouslyadhered to a patient for at least one week and each patch is configuredto support the measurement circuitry, the processor, the wirelesscommunication circuitry and the battery with the skin of the patient.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modifications, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appended claims.

1. An adherent device to monitor a patient, the device comprising: anadhesive patch to adhere to a skin of the patient; at least fourelectrodes connected to the patch and capable of electrically couplingto the patient; impedance circuitry coupled to the at least fourelectrodes to measure a hydration signal of the patient; andelectrocardiogram circuitry coupled to at least two of the at least fourelectrodes to measure an electrocardiogram signal of the patient.
 2. Theadherent device of claim 1, wherein the at least four electrodesincludes first and fourth outer electrodes located on opposite side ofthe adhesive patch and second and third inner electrodes.
 3. Theadherent device of claim 2, wherein the impedance circuitry is connectedto drive a current between first and fourth outer electrodes and measurea voltage between second and third inner electrodes.
 4. The adherentdevice of claim 3, wherein the electrocardiogram circuitry is coupled tothe first and fourth outer electrodes.
 5. The adherent device of claim4, further including a first switch and second switch connected inseries between the impedance circuitry and the first electrode andsecond electrode, wherein the first and second switch are closed whenmeasuring the hydration signal and opened when measuring theelectrocardiogram signal.
 6. The adherent device of claim 1, furtherincluding an accelerometer mechanically coupled to the adhesive patch togenerate an accelerometer signal in response to at least one of anactivity or a position of the patient.
 7. The adherent device of claim6, wherein the adhesive patch is mechanically coupled to the at leastfour electrodes, the impedance circuitry, the electrocardiogramcircuitry and the accelerometer, such that the patch is capable ofsupporting the at least four electrodes, the impedance circuitry, theelectrocardiogram circuitry and the accelerometer when the adherentpatch is adhered to the skin of the patient.
 8. The adherent device ofclaim 7, further comprising: a wireless communication circuitry coupledto the impedance circuitry, the electrocardiogram circuitry and theaccelerometer to transmit to a remote center with a communicationprotocol at least one of the hydration signal, the electrocardiogramsignal or the accelerometer signal.
 9. The adherent device of claim 8,wherein wireless communication circuitry is configured to transmit thehydration signal, the electrocardiogram signal and the accelerometersignal to the remote center with a single wireless hop from the wirelesscommunication circuitry to an intermediate device.
 10. The adherentdevice of claim 1, wherein a maximum dimension across the at least fourelectrodes comprising no more than about eight inches, such that the atleast four electrodes are capable of adhering to either a left side or aright side of the patient.
 11. The adherent device of claim 10, whereinthe maximum distance across the at least four electrodes comprises nomore than about six inches.
 12. The adherent device of claim 10, whereinthe device comprises a maximum dimension across no more than about 8inches and wherein the patch is capable of measuring theelectrocardiogram and the impedance from a left side or a right side ofthe patient.
 13. A method of monitoring a patient, the methodcomprising: adhering an adhesive patch to a skin of the patient tocouple at least four electrodes to the skin of the patient; measuring ahydration signal of the patient with impedance circuitry coupled to theat least four electrodes; and measuring an electrocardiogram signal ofthe patient with electrocardiogram circuitry coupled to at least two ofthe at least four electrodes.
 14. The method of claim 13, whereinmeasuring the hydration signal includes closing first and secondswitches to connect the impedance circuitry to one or more of theelectrodes to drive a current through the one or more electrodes. 15.The method of claim 14, wherein measuring the electrocardiogram signalincludes opening the first and second switches to disconnect theimpedance circuitry from one or more of the electrodes.
 16. The methodof claim 15, further including: measuring a signal from an accelerometerin response to at least one of an activity or position of the patient.17. The method of claim 16, wherein the adhesive patch supports the atleast four electrodes, the impedance circuitry, the electrocardiogramcircuitry and the accelerometer when the adherent patch is adhered tothe skin of the patient.